Uncomplicated cases of viral infections usually produce mild symptoms such as nasal discharge, obstruction of nasal breathing, swelling of the sinus membranes, sneezing, sore throat, cough, and headache. These symptoms generally last between one and two weeks. A mild infection is generally associated with the rhinoviruses and the coronaviruses. The uncomplicated infection is most often referred to as the “common cold.”
At present, only symptomatic treatment is available for uncomplicated viral infections, “common colds.” The treatments include the use of over-the-counter decongestants, cough suppressants, cough expectorants, aspirin, and acetaminophen. The treatments, however, do not cure or even shorten the duration of the illness. Moreover, many of the treatments have side effects such as drowsiness, dizziness, insomnia, or upset stomach. Because of the diversity of the viruses, vaccines may not be effective in preventing the onset of colds.
It has been estimated that in the course of a year, individuals in the United States suffer one billion colds. Colds thus have a tremendous societal cost in lost work days and lost school days. People suffer symptomatic discomfort. Even people receiving symptomatic treatment still suffer from some discomfort and additionally suffer side effects of treatment. Moreover, influenza affects many people, typically causing more serious symptoms than a cold.
Aldara™ (imiquimod; manufactured by 3M Corporation, St. Paul, Minn.) cream, is a prescribed patient-applied topical cream for treating external genital and perianal warts. The Aldara™ product label does not recommend using it for any other purposes.
Genital herpes is a significant health problem worldwide and continues to increase in prevalence in the United States. In individuals in the United States over 12 years old, HSV-2 seroprevalence has increased from 16.4% in 1976 to 21.8% in 1994 and is still rising. Thus, the current incidence of genital herpes caused by HSV-2 in the United States is roughly one in four or five adults, with approximately 50 million people infected with genital herpes and an estimated 0.5 million new genital herpes infections occurring each year.
HSV-2 causes periods of active disease—presenting as painful blisters containing infectious virus particles—that last 2-21 days and are followed by remission when the sores disappear. Most cases of genital herpes are asymptomatic, although viral shedding may still occur. HSV-2 is transmitted by direct contact with a sore or body fluid of an infected individual. After initial infection, the virus moves to sensory nerves, where it resides as a life-long, latent virus. The virus lies dormant in lumbrosacral that supply sensation to the genitals, perineum and upper legs.
Occasionally, these viruses reactivate and return to the area of skin infected during the primary infection. Intermittent reactivation of viral replication can result in both symptomatic and subclinical recurrences because HSV-2 can reside latently in the sensory ganglion. The reactivation rate is highly variable and very difficult to predict from individual to individual. Many believe cell-mediated immunity plays a major role in restricting reactivation yet this role is not currently well understood.
Treatments are available to reduce the symptoms and speed up the healing process of herpes infections but there is currently no cure. Antiviral drugs, such as aciclovir and valaciclovir, taken orally, reduce viral reproduction and shedding, and some topical creams, such as Docosanol and Tromantadine prevent the virus from entering the skin. Some other drugs reduce herpetic symptoms by synergising with oral antiviral medication. Cimetidine and probenecid can reduce aciclovir clearance and aspirin can reduce inflammation associated with viral infection.
While the above listed treatment methods are effective, they require constant daily dosing of medications which can be expensive. Additionally, once discontinued, the medications have no posttreatment effect and the patient immediately reverts back to pre-treatment reactivation levels. Therefore, it would be advantageous to develop a treatment for HSV-2 that would be effective in treating viral outbreaks when they occur and would reduce the rate of outbreak recurrences after the treatment is discontinued.
In 2002, Timothy W. Schacker et al. hypothesized that long term HSV-2 treatment could be achieved through enhancing the host's ability to control the virus and that topical application of imiquimod in the form of Aldara™ to herpes lesions could achieve this result. Timothy W. Schacker et al., Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study, Antimicrobial Agents and Chemotherapy, October 2002, pp. 3243-48. Schacker et al.'s hypothesis was based on the knowledge that imiquimod produces a localized immunological response in the area of skin to which it is applied as explained above and successful results in studies where imiquimod was applied to herpes lesions in Guinea Pigs. To test their hypothesis, Schacker et al. performed a phase II, randomized, double-blind, placebo-controlled study on 235 human patients. The results of the study showed that there was no statistically significant difference in outbreak recurrence times between those patients treated with imiquimod and those treated with placebo. Therefore, Schacker et al. concluded that imiquimod was not effective in reducing the rate of herpes outbreaks in humans.